Proteins can be organized into several structural classes with globular proteins the class that is most thoroughly studied and from which most structural and functional information has been derived. Other proteins are membrane-associated and are less well understood. Although globular proteins are soluble and structured in aqueous environments, and the majority of membrane associated proteins are not, most intrinsically unstructured proteins are soluble. The well-known tandem repeat proteins are families of soluble proteins of diverse primary structure involved in intermolecular interactions. We have identified a subset of repeat proteins in which an extremely high degree of sequence conservation, sometimes approaching perfection is found. In some cases, these repeats essentially constitute the entire protein, with examples of proteins having > 1000 amino acids having been found. Some proteins contain a conserved repeat region at its N- or C-terminus, or in the interior of the protein. Some proteins contain two or more different repeat component. We have termed these proteins as Monotonously Ordered Peptide Elements (MOPEs). MOPEs, or proteins with MOPE regions, appear to be present in all organisms, including viruses, but most seem to occur in multicellular organisms. They constitute a small fraction of the proteins encoded by the genome, perhaps < 1%. However, we hypothesize that the extreme degree of primary conservation suggests physiological roles of vital importance to the viability of the organism. Study of these proteins may be expected to identify critical foci for the physiological viability for multicellular organisms. Understanding these unidentified foci may provide new insight into human biology and health, and may open new targets for drug discovery against, viruses, bacteria, and metazoic parasites. In this R21 study, we propose (1) to develop a database of MOPE-related proteins to determine their distribution among organisms and to attempt to classify these proteins into related subsets, (2) to express several naturally occurring MOPEs and MOPE fragments encoded by the human genome to evaluate success of expression, solubility of protein, self-association properties, and structure where possible, and (3) modify MOPE-like proteins for the purpose of introducing self-association properties that might emulate functional properties of some MOPEs. In general, the proposed studies are designed to begin to evaluate the prospects of future studies to determine the physiological roles of particular MOPE-class proteins. [unreadable] [unreadable] [unreadable]